interleukin-8 and ciclesonide

Ciclesonide, a new inhaled corticosteroid, is administered as a parent compound and converted in the airway mucosa into the active metabolite, desisobutyryl-(des-)ciclesonide. A study was designed to evaluate the ability of ciclesonide to modulate pro-inflammatory functions of human bronchial epithelial cell (HBEC) primary cultures being converted into des-ciclesonide. HBECs were stimulated with interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha (20 ng/mL) in the presence of ciclesonide and intercellular adhesion molecule (ICAM)-1 expression, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-8 release evaluated respectively by FACS and ELISA. Ciclesonide (3 microM) significantly inhibited ICAM-1 expression by stimulated HBECs, already after 3h and still after 48 h culture (p < 0.01). At all the concentrations tested ciclesonide inhibited ICAM-1 expression (p < 0.05). GM-CSF and IL-8 release by stimulated HBECs was also downregulated by ciclesonide (p < 0.05). All the ciclesonide activities tested appeared to be mainly due to a partial inhibition of the 'IL-4 + TNF-alpha-induced' and little or no involvement of the 'constitutive' cell functions. Des-ciclesonide was detected in 24 h culture HBEC supernatants using high-performance liquid chromatography, while no parental compound ciclesonide was present. These results show at cellular level the fast and prolonged activity of ciclesonide on pro-inflammatory functions of HBECs, a selective target of asthma therapy, involved in the activation of this new inhaled corticosteroid.

Topics: Adrenal Cortex Hormones; Bronchi; Cell Survival; Cells, Cultured; Cytokines; Dose-Response Relationship, Drug; Down-Regulation; Epithelial Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-4; Interleukin-8; Pregnenediones; Tumor Necrosis Factor-alpha